Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Preparative regimen:

* Fludarabine 25 mg/m2 x 5 days start Day -6
* Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4

Apheresis cell collection (collected from the Donor Day - 8) will be enriched for FATE-NK100 per CMC. IL-2 at 6 million IU subcutaneously (SC) every other day (EOD) for 6 doses with Dose 1 on Day 0 (no sooner than 4 hours post NK cells) and last dose no later than Day +12.

FATE-NK100

Murali Janakiram, MD, MS

This is a Phase I open-label dose escalation study of a single infusion of FATE-NK100 and a short course of subcutaneous interleukin-2 (IL-2) administered after lymphodepleting chemotherapy (CY/FLU) in subjects with refractory or relapsed acute myelogenous leukemia (AML). FATE-NK100 is a natural killer (NK) cell product that is enriched for NK cells with an "adaptive", or human cytomegalovirus (CMV)-induced, phenotype. The NK cell product is comprised of peripheral blood (PB) leukocytes sourced from a related donor (HLA-haploidentical or better but not fully HLA-matched) that is seropositive for cytomegalovirus (CMV+), and enriched for adaptive NK cells by depletion of CD3+ (T-lymphocytes) and CD19+ (B-lymphocytes) cells followed by ex-vivo culture expansion.

Open Label NK Cell Infusion (FATE-NK100) With Subq IL-2 in Adults With AML

Open Label Dose Escalation Trial of an Adaptive Natural Killer (NK) Cell Infusion (FATE-NK100) With Subcutaneous IL-2 in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)

Maximum FATE-NK100 dose which could be given to 3 participants such that not more than 1 participant experienced a DLT.

Incidence of CRp defined as leukemia clearance (≤5%marrow blasts and no circulating peripheral blasts)

Incidence of CRp defined as neutrophil recovery (ANC \>500 cells/microliter) but with incomplete platelet recovery

Incidence of in vivo expansion (≥ 100 donor derived NK cells per uL blood) of NK cells

Incidence of treatment related mortality (TRM)

Incidence of minimal residual disease (MRD) clearance by bone marrow morphology after NK Cell infusion

Incidence of minimal residual disease (MRD) clearance by flow cytometry after NK Cell infusion

Incidence of Leukemia free survival (LFS)

Masonic Cancer Center, University of Minnesota

Immune System Diseases

Symptoms and General Pathology

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Neoplasm, Residual

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

GNKG168 0.25 mg/kg/day on days 1 through 5

GNKG168 0.75 mg/kg/day on days 1 through 5

GNKG168 1.5 mg/kg/day on days 1 through 5

If dose level #1 is too toxic the study will back down to dose level 0. GNKG168 0.15 mg/kg/day on days 1 through 5.

GNKG168 will be given intravenously over 1 hour on days 1 through 5 followed by 9 days of rest. Dose will be assigned at study entry.

GNKG168

Nobuko Hijiya, MD

Kirk Schultz, MD

This is a phase I trial of an investigational drug called GNKG168 in patients with relapsed and refractory acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) who are in morphologic remission but are positive for Minimum Residual Disease (MRD). GNKG168 is a Toll-like receptor (TLR) agonist. TLR agonists are a novel approach to stimulate an effective anti-tumor immune response as they are able to stimulate both innate and adaptive immune responses. There will be two strata i.e patients who have received hematopoietic stem cell transplant (HSCT) and patients who have never undergone HSCT. GNKG168 will be administered as a 60 min iv infusion. One 14-day cycle consists of 5-day treatment followed by 9 day-rest. Patients will receive 2 cycles before evaluation. The primary objective is to determine the maximum tolerated dose of GNKG168 in relapsed ALL and AML patients.

Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia

A Phase I Study of GNKG168 in Pediatric Patients With Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (IND#113600)

Therapeutic Advances in Childhood Leukemia Consortium

Associate Professor of Pediatrics

Anti-Infective Agents

Etoposide

Cytarabine

Lenograstim

Etoposide phosphate

Clofarabine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Adjuvants, Immunologic

All patients receive the same treatment regimen consisting of clofarabine, etoposide, cyclophosphamide, cytarabine, and filgrastim. Up to 4 courses of therapy may be given.

40 mg/m2/day IV over 2 hours (given at hours 0 to 2) on days 1 through 5.

100 mg/m2/day IV over 2 hours (given at hours 2 to 4) on days 1 through 5.

440 mg/m2/day IV as a 30-60 minute infusion (given at hours 4 to 5) on days 1 through 5.

Administered in Courses 1 and 2 only. 5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000 x 2 days.

Filgrastim

Given intrathecally on day 1 at the dose defined by age below:

30 mg for patients age 1-1.99 50 mg for patients age 2-2.99 70 mg for patients \>3 years of age

Paul Gaynon, MD

Clofarabine is a drug approved by the FDA (Food and Drug Administration) for treating children (age 1-21) with leukemia. This research study will use clofarabine with two other cancer fighting drugs. Clofarabine will be used together with etoposide (VePesid®, VP-16) and cyclophosphamide (Cytoxan®).

Clofarabine, etoposide and cyclophosphamide have been used together in a phase I study to find out the highest doses of these drugs that can be safely given to children with relapsed or refractory leukemia. This study is a phase II study which will use the drugs to study how well these drugs work against AML. This study will also examine the safety of this drug combination.

T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML)

T2007-002 A Phase II Study of Clofarabine With Etoposide and Cyclophosphamide in Relapsed/Refractory AML (IND 104,650)

Disease response assessed after chemotherapy from bone marrow aspirates/biopsies and complete blood count.

Genzyme, a Sanofi Company

The definition of adverse event and SAE used for data collection does not differ from that in the clinicaltrials.gov Definitions.

Patients were evaluated regularly by the treating physician.

Enrolled Patients

Baseline measures were collected for all enrolled patients.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Trial was terminated early due to loss of funding and concern that accrual goals could not be met. All six patients enrolled were deemed evaluable toxicity. No analysis was conducted on the study outcome variables.

Peggy Romano, BA, CCRP

All patient that completed at least 1 treatment course.

Patients that completed at least 1 treatment course of study drug.

Achievement of Complete Remission (CR) at Reinduction

Death

All patients receive the same treatment regimen consisting of clofarabine, etoposide, cyclophosphamide, cytarabine, and filgrastim.

clofarabine: 40 mg/m2/day IV over 2 hours (given at hours 0 to 2) on days 1 through 5.

etoposide: 100 mg/m2/day IV over 2 hours (given at hours 2 to 4) on days 1 through 5.

cyclophosphamide: 440 mg/m2/day IV as a 30-60 minute infusion (given at hours 4 to 5) on days 1 through 5.

filgrastim: 5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000 x 2 days.

cytarabine: Given intrathecally on day 1 at the dose defined by age below. 30 mg for patients age 1-1.99 50 mg for patients age 2-2.99 70 mg for patients \>3 years of age

Single Arm - Protocol Chemo Regimen

Treatment Course 1

Treatment Course 2

Treatment Course 3

Treatment Course 4

Neoplasm Metastasis

Analgesics

Interleukin-2

Mesna

Denileukin diftitox

Analgesics, Non-Narcotic

Patients are treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Given by infusion on Day 0. The product is T cell-depleted (CD3-) and B cell-depleted (CD19). Target dose for infusion is \< or = 8 x 10\^7 nucleated cells/kilogram.

Natural Killer Cells

Administered as a 1 hour intravenous infusion once a day for 5 doses beginning on day -6.

Administered as a 2 hour intravenous infusion with high volume fluid flush and mesna per institutional guidelines on day -5 and -4 one hour after fludarabine infusion. (Day -4 administration may be omitted if patient has had a transplant in the previous 4 months.)

12 ug/kg/day will be administered on day -1 and day -2 intravenously.

Day -1 before planned NK cell infusion, the donor will undergo lymphapheresis (Removal of lymphocytes from donated blood, with the remainder of the blood retransfused into the donor).

Donor lymphapheresis

Administered after NK cell infusion, 10 million units every other day for a total of 6 doses. (Patients weighing less than 45 kilograms will receive a dose of 5 million units/m\^2 every other day for 6 doses).

IL-2

Jeffrey S. Miller, M.D.

This is a phase II therapeutic study of related donor HLA-haploidentical NK-cell based therapy after a high dose of fludarabine/cyclophosphamide with denileukin diftitox preparative regimen for the treatment of poor prognosis acute myelogenous leukemia (AML).

Patients achieving a complete remission and neutrophil recovery (ANC \> 500) for at least 4 weeks will be considered for allogeneic transplant to prolong remission (independent of this study).

All patients, including those who go on to transplant, will be followed to determine disease free survival, treatment related mortality, and time to relapse.

Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)

Adoptive Transfer of Haploidentical Natural Killer Cells to Treat Refractory or Relapsed AML MT2010-02

The primary objective of this study was to estimate the incidence of in vivo expansion of natural killer (NK) cells 14 days after infusion of an allogeneic donor product enriched for NK progenitors. Successful in vivo donor NK cell expansion was defined by measuring an absolute circulating donor-derived NK cell count of \>100 cells/ul in the patient's peripheral blood 14 days after infusion.

Disease response was defined as complete remission (disease response) by morphologic criteria including \<5% blasts in a moderately cellular or cellular marrow. Complete remission was also correlated with NK cell expansion in vivo, IL-15 levels and donor/recipient KIR B genotyping, and Treg depletion.

Number of patients alive and disease free at 6 months. The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

Number of patients who have had a relapse(the return of disease after its apparent recovery/cessation) after obtaining a complete remission of their disease.

Number of patients who died within the first 100 days of treatment due to toxicity.

Association between in vivo natural killer (NK) cell expansion and complete response without platelet recovery (CRp) with donor killer immunoglobulin-like (KIR) genotype and Treg depletion. In vivo donor NK cell expansion was correlated with regulatory T-cell (Treg) depletion as detected on flow cytometry.

Due to chemotherapy as prep for the NK cell infusion, it is expected that all patients will experience severe depression of their blood counts and other related toxicities. Adverse event (AE) collection will focus on targeted AEs and unexpected AEs at specific time points in relation to the NK cell infusion and IL-2 injections.

Patients with acute myeloid leukemia (AML) are treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Treated Patients

Evaluable (Treated) Patients

Age, Continuous

United States

Region of Enrollment

Patients with acute myeloid leukemia (AML) were treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Percent of Patients With Successful Expansion of Natural Killer Cells After Infusion

Percent of Patients With Complete Remission of Disease

Percent of Patients With Disease Free Survival

Percent of Patients With Incidence of Relapse

Number of Patients With Treatment-Related Death

KIR matched: Patients with acute myeloid leukemia (AML) were treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Evaluable (Treated) Patients (Expansion=No)

KIR mismatched: Patients with acute myeloid leukemia (AML) were treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Evaluable (Treated) Patients (Expansion=Yes)

Percent of Patients With Natural Killer Cell Expansion Versus KIR Genotype Versus Treg Depletion

Overall Study

Nine pre-defined dose levels for specific subsets of subjects will be administered by IV (in the vein). PR104 will be administered initially as induction therapy followed by administration as consolidation therapy, as is typical of established treatment regimens in AML.

PR104

The current understanding of PR104 justifies the evaluation of PR104 in subjects with relapsed/refractory AML and ALL. These include:

* Hypoxia. Leukemic bone marrow is likely to demonstrate a level of hypoxia sufficient to activate PR104 to its active metabolites PR104H and PR104M.
* Myelotoxicity as the primary toxicity at MTD. In prior clinical studies in subjects with solid tumors PR104 has demonstrated myelotoxicity as the primary toxicity. This observation suggests that PR104 will exert a similar effect on leukemic cells.
* AKR1C3. AML has been reported to exhibit high levels of AKR1C3 which should lead to selective activation of PR104 within both hypoxic and oxic leukemic cells.
* Preclinical data. PR104 has demonstrated impressive activity in an initial study using primary human ALL in a mouse model.

The initial dose finding phase of the study will provide estimates of the activity and toxicity of PR104 in subjects with refractory/relapsed AML, and determine the optimal individualized dose to give each subject based on his/her covariates (prior CR duration, prior number of salvage therapies, age). Once a potentially beneficial dose has been determined, an expanded cohort of subjects with AML or ALL will receive PR104 at a uniform dose. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity and acceptable safety in AML to warrant future phase II or phase III studies in this indication.

Primary objectives

* Determine the toxicities and recommended dose of PR104 when administered IV to subjects with relapsed/refractory AML and ALL.

Secondary objectives

* Evaluate the pharmacokinetics (PK) of PR104 and a series of PR104 metabolites
* Evaluate any anti-tumor effects of PR104
* Evaluate the expression of AKR1C3 in bone marrow and leukemic cells
* Evaluate potential biomarkers of hypoxia

A single arm study defining the recommended dose of PR104 for each subpopulation in this patient population.

Following informed consent, subjects will undergo baseline evaluation with a history, physical exams, blood work, and disease assessment. Subjects will be assigned a dose of PR104 based on a Bayesian model maintained at the Statistical department at MD Anderson Cancer Center. The model will be updated with both toxicity and efficacy data as it is generated for each subject. New subjects will receive the currently predicted best dose for their respective subset based on prior treatment, age and duration of prior response.

PR104 will be administered initially as induction therapy for up to 3 cycles. Response will be assessed around day 42 (+/- 2 days) of the study. Subjects who obtain a CR or CRp will receive consolidation therapy for up to 4 additional cycles.

Subjects will be evaluated each week during the induction phase of the study. During the consolidation phase of the study, subjects will be evaluated on Day 1 of each cycle and as clinically indicated. Subjects with clinically significant progression will be removed from study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Open Label NK Cell Infusion (FATE-NK100) With Subq IL-2 in Adults With AML	NCT03081780	Refractory Acut... Relapsed Acute ...	FATE-NK100	18 Years - 70 Years	Masonic Cancer Center, University of Minnesota
Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia	NCT01743807	Relapsed Acute ... Relapsed Acute ...	GNKG168	1 Year - 21 Years	Therapeutic Advances in Childhood Leukemia Consortium
T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML)	NCT00939653	Relapsed Acute ...	Clofarabine Etoposide Cyclophosphamid... Filgrastim Cytarabine	1 Year - 21 Years	Therapeutic Advances in Childhood Leukemia Consortium
Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)	NCT01106950	Leukemia, Myelo...	Natural Killer ... Fludarabine Cyclophosphamid... Denileukin dift... Donor lymphaphe... IL-2	2 Years -	Masonic Cancer Center, University of Minnesota
Open Label NK Cell Infusion (FATE-NK100) With Subq IL-2 in Adults With AML	NCT03081780	Refractory Acut... Relapsed Acute ...	FATE-NK100	18 Years - 70 Years	Masonic Cancer Center, University of Minnesota
PR104 in Treating Patients With Refractory/Relapsed Acute Leukemia	NCT01037556	Acute Myelogeno... Acute Lymphocyt...	PR104	18 Years -	Proacta, Incorporated

Spots Global Cancer Trial Database for relapsed acute myelogenous leukemia